1. Field of the Invention
The present invention relates to an immobilizing device or method.
2. Related Art Statements
Nowadays, films (thin layers) immobilized biological macromolecules or functional polymers have been widely utilized in an analytical instrument, such as a biochip or a biosensor. In addition, films of functional macromolecules or dyes have been used in various types of leading-edge display devices, optical devices, or semiconductor devices.
Although there has been developed and practically used various devices and techniques for forming such films or thin layers, such conventional devices and methods have not always been applicable to immobilize or deposit biomolecules or of functional macromolecules and to form such films in which activities and functionalities of them are kept due to following reasons.
For example, there are conventional sputtering devices, Electron Beam (EB) resistance heating type vapor deposition sputtering devices, and chemical vapor deposition apparatuses, and they are practically used for forming films of metals or inorganic compounds. However, since in such devices a substance contained in the films must be exposed to plasma or high temperature under high vacuum, if the substance to be processed is biological macromolecules or organic macromolecules it is almost impossible to immobilize or deposit the substance to form a film or a thin layer in which the activities and functionalities of that are kept.
Conventional electrostatic spray apparatus is apparatuses capable of spraying a liquid using pressurized air to deposit the sprayed liquid onto a substrate by electrostatic forces, and it is widely used in coating industry. However, since the conventional electrostatic spray device needs a large amount of liquid due to spraying by pressurized air, almost splayed liquid is wasted. Therefore, such conventional electrostatic spray apparatus is not applicable to form a thin layer of a very small amount of functional macromolecules or biological macromolecules. In addition, since, when a liquid is sprayed using pressurized air the splayed droplets have very large diameters, the splayed droplets will arrive on a substrate without drying. Thus it takes long time to dry the sample contained in the splayed liquid on the substrate, if biological macromolecules, which tend to be denatured or modified in such a long time drying process, are to be sprayed, the splayed biomolecules are most likely to be damaged. Therefore, in the conventional electrostatic spray apparatus, it is hard to immobilize such a substance having a damageable property and to form a thin film in which activities and functionalities of it are retained.
In a conventional spotting device or a coater, solutions are spotted or coated on a substrate using either a pin-like tool made of a metal capable of holding the solutions in a gap like a grove in a fountain pen tip or a coater, and the spotted or coated solutions are dried to form a film. Due to the same reasons i.e., needs of a long time drying process as mentioned about the electrostatic spray apparatus, in the conventional spotting device and coater it is difficult to form a film or a thin layer of substances such as bio macromolecules having properties in which its activities can easily be damaged.
A conventional ink jet method is a method for emitting a jet of a solvent in which target functional polymers are dissolved as minute droplets from a nozzle, to deposit them onto a substrate, and to dry them to form a thin layer. However, due to the same reasons i.e., needs of a long time drying process as the above mentioned techniques, in this method it is impossible to immobilize or deposit to form a thin layer retaining its activities and functionalities of substances such as functional polymers.
The Electro Spray Deposition (ESD) technique is a technique for electrostatically spraying sample solutions to deposit them onto a substrate to form a film, and this ESD technique is disclosed in PCT international publication WO98/58,745. This technique is much more suitable for making a film of substances such as bio macromolecules than other conventional techniques and can form a thin layer retaining its activities or functionalities depending on conditions. However, this technique cannot spray solutions when electrical conductivity of the solution is high and thus there is a problem that films or thin layer which can be formed using this technique are limited to some kinds of samples (refer to a document “Analytical Chemistry, Vol. 73”, pp. 2183-2189, 2001). In general bio macromolecules, especially proteins, are dissolved in a buffer solution so as to keep PH constant, electrical conductivity of that is equal to or greater than approximately 1000 μS, and thus in the ESD method it is impossible to immobilize or deposit such sample solutions to form a spots, films or thin layers. In addition, proteins or the like may rapidly lose its activities or functionalities for a short time if a stabilizer such as a buffering agent is removed. When such samples are used for forming s film in the ESD method, if once a buffering agent is removed, a process for making a film must be completed for a short time and thus an operation efficiency will be down. In addition, there is a problem that finished films may have lower activities of samples even if the operations for forming films are done in a hurry. In addition, in the ESD method, in order to pass through a tube of a capillary tip, samples are must almost absolutely be dissolved in a solution. Therefore, in this ESD method, it is impossible to use samples such as particles having a low solubility. Additionally, since the ESD method is a method for spraying solutions as minute droplets utilizing only electrostatic forces of the droplets, a spraying rate is very slow and thus manufacturing speed of the chips or films is slow.
Although it is well known that there has been developed various atomizers or splay devices using different vibrating or oscillating elements for many kinds of purposes, they are just for splaying or atomizing, there has been no attempt to use these vibrating elements as an immobilizing or depositing device.
In order to deposit and immobilize bio macromolecules (such as proteins) or functional polymers to form spots or films while the biologically activities or functionalities of the substances are retained, it is necessary to immobilize and form a film of the substances such that these substances are kept in a condition on which the substance cannot easily be denatured or altered. However, the conventional ESD method or device mentioned above cannot keep such a condition while forming the film. One of the conditions on which the substance cannot easily be denatured or altered is that a liquid containing the substances such as bio macromolecules is extremely quickly dried. However, in general, a liquid at normal temperature is slowly evaporated and the liquid coated on a substrate is not rapidly evaporated even if with vacuum. Although one of the methods for rapidly drying a liquid is that the liquid containing target samples is heated, there is a problem that almost bio macromolecules and functional polymers are altered or denatured by heat treating, and thus biological activities and functionalities of that may be damaged.
Although there is a conventional method, such as a freeze dry, for making a solid from solution containing bio macromolecules and the like, according to this freeze dry method it is impossible to form a film if it is frozen and the frozen substances will normally transform into fine particles. In addition, in case of bio macromolecules or the like which must be dissolved in a buffering solution, or an organic polymers, which have high electrical conductivities, since they have high conductivity, they cannot be processed even by the ESD method and thus it is impossible to form a film of them.
Namely, in any conventional methods or devices it is impossible to form a film of bio macromolecules or functional polymers, in the form of a desired shape or thickness without loosing biological activities or functionalities of that, from small amount of substances.